The effectiveness of glatiramer acetate in clinical practice: an observational study.

AIM: To evaluate the clinical effectiveness and safety of glatiramer acetate for use in routine clinical practice. PATIENTS AND METHODS: A retrospective, observational study was conducted on patients with multiple sclerosis who were treated with glatiramer acetate in clinical practice. The primary outcome was the clinical effectiveness of glatiramer acetate treatment. RESULTS: The study included a total of 104 patients (women, 59.6%; age at onset of glatiramer acetate treatment, 39.9 ± 10.9 years; prior treatment for multiple sclerosis, 30.8%). The patients had received glatiramer acetate treatment for an average of 3.6 ± 1.9 years. During the first year of glatiramer acetate treatment, the relapse rate decreased by 60%. At this time, the number of relapses had decreased for 47 patients (45.1%), 67 patients (68.4%) had not suffered a relapse and 78 patients (75.0%) showed no signs of progression. During the second year of glatiramer acetate treatment, the relapse rate decreased by 70%. At this time, the number of relapses had decreased for 43 patients (41.3%), 63 patients (75.9%) had not suffered a relapse and 59 patients (56.7%) showed no signs of progression. There were no reported relapses or progression in 56 patients (53.8%) and 41 patients (39.4%) during the first and second years of treatment, respectively. Discontinuation of glatiramer acetate was necessary in only three patients. The most common adverse effects included fatigue (28.9%) and spasticity (7.7%). CONCLUSION: This evaluation of glatiramer acetate use in clinical practice supports the effectiveness and the safety profile observed in previously published clinical trial studies.

TRAIL/TRAIL receptor system and susceptibility to multiple sclerosis.

The TNF-related apoptosis inducing ligand (TRAIL)/TRAIL receptor system participates in crucial steps in immune cell activation or differentiation. It is able to inhibit proliferation and activation of T cells and to induce apoptosis of neurons and oligodendrocytes, and seems to be implicated in autoimmune diseases. Thus, TRAIL and TRAIL receptor genes are potential candidates for involvement in susceptibility to multiple sclerosis (MS). To test whether single-nucleotide polymorphisms (SNPs) in the human genes encoding TRAIL, TRAILR-1, TRAILR-2, TRAILR-3 and TRAILR-4 are associated with MS susceptibility, we performed a candidate gene case-control study in the Spanish population. 59 SNPs in the TRAIL and TRAIL receptor genes were analysed in 628 MS patients and 660 controls, and validated in an additional cohort of 295 MS patients and 233 controls. Despite none of the SNPs withstood the highly conservative Bonferroni correction, three SNPs showing uncorrected p values<0.05 were successfully replicated: rs4894559 in TRAIL gene, p = 9.8×10(-4), OR = 1.34; rs4872077, in TRAILR-1 gene, p = 0.005, OR = 1.72; and rs1001793 in TRAILR-2 gene, p = 0.012, OR = 0.84. The combination of the alleles G/T/A in these SNPs appears to be associated with a reduced risk of developing MS (p = 2.12×10(-5), OR = 0.59). These results suggest that genes of the TRAIL/TRAIL receptor system exerts a genetic influence on MS.

Killer cell immunoglobulin-like receptor genes in Spanish multiple sclerosis patients.

Killer cell immunoglobulin-like receptors (KIRs) are regulators of cytolytic activity of natural killer and certain T cells through interactions with human leukocyte antigen (HLA) class I ligands. KIRs have been shown to contribute to the pathogenesis of several autoimmune diseases, but their role in multiple sclerosis (MS) is still unclear. Here we determined the influence of KIR genes and their HLA class I ligands on susceptibility to MS and on the response to interferon-beta treatment in a Spanish population. KIR and HLA genotyping were performed in 200 MS patients and 200 controls. Significantly higher frequencies were found for KIR2DL5 and KIR3DS1 genes in MS patients and the carriage of the KIR2DL1 gene was associated with a higher progression index. Moreover, the frequency of the HLA-Bw4 motif was significantly reduced in MS patients. The KIR2DL1 and HLA-C2 matches were more frequent in MS patients, whereas the KIR3DL1 and HLA-Bw4 matches were more frequent in healthy controls. Nevertheless, non significant associations were found between all the KIR genes and therapeutic response to interferon-beta. Our results confirm that the carriage of HLA-Bw4 is a protective factor in MS and suggest that KIR2DL5 and KIR3DS1 may have a predisposing role in the disease.